JP2021529217A - Bioabsorbable drug transfer capsule for subcutaneous insertion - Google Patents

Abstract

The bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention is inserted into the subcutaneous biostructure to transmit the active ingredient, thereby forming a storage space for accommodating the active ingredient, and the active ingredient leaks to the outside. The casing is configured to include a casing for blocking the containment space from the outside so that the active ingredient in the containment space is discharged to the outside by being decomposed in the biological assembly. It is made of a bio-absorbent material so that it can be absorbed into the body after it is allowed, and it is effective in the body in a predetermined cycle and number of times with one insertion without inconvenience such as multiple additional inoculations. The ingredients can be made to work.

Description

The present invention relates to a drug transfer capsule, which is a capsule type and is a new form of drug transfer system for transmitting an active ingredient such as a drug to the biostructure by being inserted directly into the skin or muscle under the skin. A storage space for an active ingredient such as a drug is formed in the body, and the outer casing is made of a bioabsorbable material, which has a function of starting transmission of the drug only after a predetermined time has passed. It concerns drug transfer capsules.

Vaccine is a term derived from the Latin word vacca, which means "cow" borrowed by Jenner who found the cowpox method, and the immunity that can be obtained by successful vaccination is body fluid. It includes two types of immunity (Humoral immunity, antibody-mediated immunity, antibody-mediated immunity) and cell-mediated immunity (Cellular, cell-mediated immunity).

That is, the goal of vaccination is not only humoral immunity, which is the ability to respond immediately when an antibody is produced at the time of vaccination, which is generally known, and then the pathogen invades, but also the pathogen. When a pathogen invades the pathogen, it releases all the cell-mediated immunity that induces the action of T lymphocytes that directly attack the pathogen by releasing the cytokine (Cytokine), which is an inflammation-inducing substance. be.

Immunity obtained through the antibody received from the mother immediately after birth or by administering an anti-serum containing the antibody is passive immunity, which is vaccine-induced immunity against having a temporary effect. Is active immunity because it allows the immunizer to remember the pathogen.

With such a vaccine, the antibody-forming effect is reduced by only one inoculation, so one inoculation is not enough, and complete immunity is generated only by two or three (or more) inoculations. However, this is all the same in the case of a whole cell vaccine (Whole-cell vaccine) made by utilizing the whole pathogen and a constituent unit vaccine (Acellular or subunit vaccine) using only a part of the pathogen.

The majority of vaccines are whole-cell vaccines and are reclassified as either inactivated (inactivated vaccines) or attenuated (live vaccines) so that they cannot manifest their pathogenicity. Inactivated vaccines use chemicals and radiation to remove the vitality of pathogenic microorganisms, so they are stable and have the advantage of not reappearing pathogenicity in the human body, but they are less effective and are given several additional doses. There is a need.

On the other hand, live vaccines are those in which pathogenic microorganisms are cultivated in an extreme environment or cultivated while continuously transferring the host to weaken the toxicity, and when administered to a person with weakened immune function, the pathogenicity is restored. However, it may induce the infectious disease, but has the advantage that antibody formation can be completed with a smaller number of inoculations than the inactivated vaccine.

That is, the route of administration of the vaccine is determined in the form of intramuscular injection, except in exceptional cases such as oral preparations for infants such as oral pediatric paralysis vaccine, but this is a rare experience for vaccinated persons. There is the inconvenience of having to inoculate several times at intervals of several months to several years with such an injection method.

Apart from this inconvenience of the inoculator, infectious diseases of livestock cause a big problem in large-scale pastoral farmers who keep dozens to hundreds of livestock, so it is appropriate depending on the age of each livestock. It is recommended or compulsory to inoculate several times at the right time, which is very annoying and difficult.

For example, in the case of foot-and-mouth disease, which has been infected with cattle, pigs, goats, deer, etc. and has been a problem repeatedly over a long period of time, it can be prevented by inoculating the foot-and-mouth disease vaccine twice or more. It is not only difficult to manage several inoculations of each individual at accurate intervals, but also weeks to months after the first inoculation, the age and age are high and the power is good. Inoculating a large number of livestock more than once carries the risk of safety accidents.

Therefore, there is a need for a technique that does not require additional inoculation so that sufficient antibodies can be formed in livestock of younger weeks and months with only one inoculation, but an appropriate solution has been proposed. There is no actual situation.

As one of such solutions, the present inventor absorbs water from the living body so that the active ingredient such as a vaccine can act appropriately in the living body at a predetermined time interval from the time of the first inoculation through the present invention. I have been researching capsules for transmitting active ingredients using sex materials.

As a technique structurally related to the present invention, the needle part (named as a bullet) of a microneedle attached to the skin in a patch type is left on the skin, and the drug is injected into the skin by biodecomposition of the bullet. The technology for transmission has been disclosed in Korean Patent Application No. 10-2014-0053907 "Micro-bullet for drug transmission", but this document is a concept of controlling the release rate and amount of a drug by the biodegradation rate or the like. The present invention is particularly aimed at, apart from effective insertion techniques and drug transmission techniques, by merely presenting specific means for the effects to the extent of "conical bullets". It does not present or imply any concrete composition related to "a technique for enabling the active ingredient to act on the internal structure after a predetermined time of several weeks to several months".

Therefore, in order to improve the conventional drug transmission method that requires repeated inoculation or the like, the present invention provides a casing so that the drug can be transmitted into the body only after a predetermined period of time intended from the time of initial insertion. A bio-absorbent drug transfer capsule for subcutaneous insertion that regulates the decomposition rate of the casing wall in a specific area that communicates with the outside, and eventually all components including the casing are absorbed into the body and do not need to be removed separately. The purpose is to provide.

Another object of the present invention is for a drug that should be repeatedly applied for the exact period required for each component infused, such as a vaccine or an absorptive drug, with a single insertion as desired for each drug. It is to provide a bioabsorbable drug transfer capsule for subcutaneous insertion that allows it to act in the body in cycles and times.

Another object of the present invention is to provide a bioabsorbable drug transfer capsule for subcutaneous insertion, which is provided with a means that can be accurately inserted at a required position such as the inside of the skin or muscles.

In order to achieve the above-mentioned object of the present invention, the bioabsorbable drug transfer capsule according to the present invention is inserted into the subcutaneous biological structure to form a storage space for containing the active ingredient in order to transmit the active ingredient. The active ingredient is configured to include a casing for blocking the containment space and the outside so that the active ingredient is not leaked to the outside, and the casing is decomposed in the biological assembly to form the effective effect in the containment space. It is formed of a bioabsorbable material so that it can be absorbed into the biostructure after allowing the components to flow out.

At this time, the bioabsorbable material of the casing of the bioabsorbable drug transfer capsule for subcutaneous insertion contains a biodegradable metal represented by the following chemical formula 1.

[Chemical formula 1]
Mg _a Zn _b X _c

In Chemical Formula 1, a, b and c are% by weight of each component, a + b + c = 100% by weight, and a or b is the most in the range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, 0 ≦ c ≦ 40. Broadly, X is one or more selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.

At this time, in the chemical formula 1, a, b and c are% by weight of each component, a + b + c = 100% by weight, and i) 90 ≦ a ≦ 100, 0 ≦ b ≦ 10, 0 ≦ c ≦ 40 or ii. ) 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 40, and X is one or more selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P. ..

At this time, the biodegradable metal may be pure Mg containing unavoidable impurities.

At this time, the biodegradable metal may be pure Zn containing unavoidable impurities.

On the other hand, at least a part of the casing is a metal region formed of the biodegradable metal, and the active ingredient in the accommodation space is the earliest outside in the metal region in the process of decomposing the bioabsorbable material. A primary leak point is formed, and the active ingredient leaks sequentially after the primary leak point leaks to another point of the casing including the metal region (n is 2). The above integers) can be formed.

At this time, at the primary leakage point or the nth-order leakage point, the biodegradable metal such that two or more metal phases (phases) generate a galvanic circuit according to the chemical formula 1 to accelerate the decomposition rate. It can be formed by appropriately arranging the component composition of the above in the metal region.

Further, the primary leakage point or the nth leakage point is the point where the thickness of the casing wall is the thinnest by adjusting the thickness of the casing wall between the accommodation space of the casing and the outside. It can be a primary leak point, and the nth leak point can be sequentially formed depending on the thickness of the casing wall.

At this time, the accommodation space including the primary leakage point or the nth leakage point was isolated in the casing corresponding to the primary leakage point or the nth leakage point, respectively, so that the active ingredient could not communicate with each other. Space can be formed.

The bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention has a tip portion formed of the biodegradable metal, an inflated portion formed of a soft biodegradable polymer material, and at least one end of the inflated portion. It is configured to include at least one or more nodules formed of the biodegradable metal to be linked, the inflated portion being formed internally in a tube or pocket shape capable of accommodating the active ingredient and both ends. It can have a structure in which the tip portion or the nodule portion is connected so as to communicate with each other.

At this time, the tip portion has a tip that can pierce the skin in the process of being inserted subcutaneously, and the nodule portion has an injection port capable of injecting the active ingredient and the injected active ingredient flows out to the outside. A backflow prevention means can be provided to prevent this from occurring.

At this time, the injection port of the nodule has a tubular shape through which the injection needle can be penetrated so that it can be used in a form attached to the injection needle of a drug injection means such as a syringe. The backflow prevention means has a backflow prevention valve structure such as an elastic membrane that prevents the active ingredient injected from the drug injection means from flowing out after the injection needle is removed, and the expansion portion of the tip portion thereof. An injection needle anchoring portion can be provided inside the connecting portion with the injection needle so that the skin insertion direction of the tip portion is stably fixed by mounting the injection needle.

At this time, the expanded portion is composed of polydioxanone (PDO), polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), glycolide-L-lactic acid copolymer (PGLA) and glycolide-caprolactone. It may be one or more biodegradable polymer materials selected in the group consisting of copolymers (PGCL).

With the above configuration, the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention has the following effects.

First, the casing is manufactured from a material that is decomposed and absorbed in the living body, and the active ingredient such as a vaccine is injected into the storage space inside the casing before the insertion of the living body, and at the same time, the wall of the casing is decomposed. By appropriately setting the time it takes for the vaccine in the containment space to flow out to the external biological organization based on the theory of adjusting the decomposition rate of the biodegradable metal and the experimental results, there is no inconvenience such as multiple additional inoculations. The amount of drug released over time can be adjusted by multiple insertions, or the active ingredient can be made to act in vivo at a predetermined cycle and number of times.

Second, since the entire capsule casing is made of a bioabsorbable material, it is decomposed and absorbed in the biostructure such as subcutaneous muscles, so it must be removed after use like a conventional internal contraceptive device. The pain and complexity that must be avoided can be avoided.

Third, unlike products used for oral use, the core is to secure the hardness that can pierce the skin for insertion into the living body, and biodegradable metal that can form high hardness apex. By applying with the material of the casing, it is easy to insert it to a desired position in the body.

Fourth, the structural features of the capsules provided facilitate insertion into the body by providing the appropriate auxiliary means necessary for the insertion together.

It is a phase diagram based on the content of magnesium, zinc and calcium of biodegradable metals that can be applied to the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention. It is a phase diagram based on the content of magnesium, zinc and calcium of biodegradable metals that can be applied to the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention. It is a phase diagram based on the content of magnesium, zinc and calcium of biodegradable metals that can be applied to the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention. It is a graph which measured the decomposition rate of the metal sheet manufactured by one embodiment of this invention. It is a sample photograph of a bioabsorbable drug transfer capsule for subcutaneous insertion according to the first embodiment in a preferred embodiment of the present invention. FIG. 5 is a drawing of a bioabsorbable drug transfer capsule for subcutaneous insertion according to a second embodiment in a preferred embodiment of the present invention. FIG. 5 is a drawing of a bioabsorbable drug transfer capsule for subcutaneous insertion according to a third embodiment in a preferred embodiment of the present invention. It is a figure explaining the process for applying a drug transfer capsule by an Example of FIG. 7 in a living body. As a modification of the embodiment of FIG. 7, it is a drawing of the bioabsorbable drug transfer capsule for subcutaneous insertion according to the fourth embodiment. It is a graph which compared the experimental result of the antibody formation effect at the time of the injection of the porcine foot-and-mouth disease vaccine by the capsule insertion of the 1st Example of this invention with the conventional injection method. It is a graph which compared the experimental result of the antibody formation effect at the time of the injection of the porcine foot-and-mouth disease vaccine by the capsule insertion of the 1st Example of this invention with the conventional injection method.

Hereinafter, the configuration of the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention described above will be described in more detail with reference to the drawings showing examples and the like.

On the other hand, in the above and the following description, it should be understood that the "active ingredient" includes various drugs that conventionally require repeated inoculation, and a vaccine can be mentioned as an example thereof. A good example is the foot-and-mouth disease vaccine, but it is not limited to this. In addition to the vaccine, it can include all drugs that require repeated inoculation of two or more times in a predetermined period of time, such as an internal repellent.

The most fundamental property of the present invention is that, among bioabsorbable materials, a biodegradable metal having excellent strength enough to be commercialized as a bone fixing screw or other in-vivo implant material is applied to the capsule material under the skin. Not only is it easier to insert into the biostructure, but by applying the biodegradable metal degradation rate control technique revealed through years of research by the inventor of the present invention, the desired suitability. The present invention relates to a technique for preventing the active ingredient in the capsule storage space from leaking to the outside after a lapse of time.

That is, as disclosed multiple times through Korean Patent Application No. 10-2017-0044692 "Microneedle using biodegradable metal" or Korean Patent Application No. 10-2017-0045449 "Biodegradable Metal Implant". In addition, the inventor of the present invention is constantly researching the regulation of the decomposition rate of biodegradable metals containing magnesium and zinc as the main components and the improvement of other physical properties, and some of the contents already disclosed have been disclosed. It applies to the present invention.

Thereby, in the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention, at least a part of the casing for preventing the leakage of the active ingredient between the storage space and the outside is decomposed in the biostructure. It can be produced from a biodegradable metal containing at least one or more metals selected from Mg and Zn that are decomposed by generating hydrogen gas by the following chemical formula as a main component.

Mg + 2H ₂ O → Mg (OH) ₂ + H ₂ (gas)

Zn + 2H ₂ O → Zn (OH) ₂ + H ₂ (gas)

That is, in the present invention, the metal region of the bioabsorbable drug transfer capsule for subcutaneous insertion can be produced by using magnesium (Mg), zinc (Zn) or the like as a single material, but also at this time, unavoidable impurities are added. It may contain a small amount.

As described above, the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention can also be provided with a single biodegradable metal material, with a region formed of the biodegradable metal and a biodegradable polymeric material. The formed regions can also be provided in a combined structure.

When provided in a structure combined with a biodegradable polymer material part, a tip to penetrate the skin, a finish to seal the containment space, etc. can be manufactured as metal regions. Further, it can be manufactured so that a primary or n-order leak point is provided in the metal region to accurately identify the time point at which the active ingredient in the containment space, such as a vaccine, is leaked.

In addition, the biodegradable polymer material part, which is applied to enable the entire capsule from which all the active ingredients have been removed to be decomposed and absorbed in the biostructure, has also been conventionally used as a bioabsorbable material. Well-known polydioxanone (PDO), polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), glycolide-L-lactic acid copolymer (PGLA), glycolide-caprolactone copolymer (PGLA) PGCL) and the like can be applied, but unlike the biodegradable metals described above, these polymer materials have soft and flexible properties, and thus have a useful effect in relation to the expansion of the capacity of the active ingredient. Can be given. This will be described in more detail with reference to the following preferred embodiments of the present invention.

Regarding the above-mentioned technique for adjusting the decomposition rate of a biodegradable metal, the biodegradable metal is represented by the following chemical formula 1, and after being inserted into a subcutaneous biostructure, it is absorbed and decomposed to form magnesium or zinc metal ions. It can be configured to be a biodegradable metal that releases the degradation products into the body.

[Chemical formula 1]
Mg _a Zn _b X _c

In Chemical Formula 1, a, b and c are% by weight of each component, a + b + c = 100% by weight, and a or b is the most in the range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, 0 ≦ c ≦ 40. It is preferable that X is at least one selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.

The biodegradable metal applied to the bioabsorbable drug transfer capsule for subcutaneous insertion preferably contains the most magnesium or zinc. Therefore, in the above chemical formula 1, a, b and c are% by weight of each component, and a + b + c = 100% by weight, i) 90 ≦ a ≦ 100, 0 ≦ b ≦ 10, 0 ≦ c ≦ 40 or ii). 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 40, and X is one or more selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P. Is preferable.

That is, in the present invention, the bioabsorbable drug transfer capsule for subcutaneous insertion is an active ingredient that intends to act in vivo by generating a galvanic circuit of a plurality of metal components using two or more metals as a material by the above chemical formula. It can also be adjusted so that the decomposition rate of the casing within the biostructure can be adjusted according to the purpose of (vaccine, etc.).

1 to 3 are state diagrams based on the contents of magnesium, zinc, and calcium, and the displayed numbers 2 to 7 are the sample numbers of the experimental examples described later, and as shown, magnesium, zinc, and calcium are the numbers thereof. It can exist in various states depending on the content, and _{intermetallic compounds such as Mg 2} Ca (C14_B), Ca ₂ Mg ₆ Zn ₃ , and Mg Zn generate galvanic circuits compared to when they are single materials. The decomposition speed can be increased.

The biodegradable metal applied to the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention has another type of second metal on the surface of the biodegradable metal represented by the chemical formula 1 in order to generate a galvanic circuit. It can also have a coated structure, where the second metal is sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver. , Gold, manganese, calcium, etc., but are not limited to this. At this time, when producing a biodegradable metal using the iron (Fe), the stainless steel component must not be contained.

The experimental basis for the rapid increase in decomposition rate when an intermetallic compound phase such as _{Mg 2} Ca (C14_B), Ca ₂ Mg ₆ Zn _{3, and Mg Zn is formed is supported through Experimental Example 1 below.}

In this way, the present invention uses the results obtained through experiments under various conditions to determine the decomposition rate of biodegradable metals in various compositions under the same environment in the living body, and the present invention is made at an appropriate time and in an appropriate amount. Further, the present invention provides a bioabsorbable drug transfer capsule for subcutaneous insertion capable of repeatedly transmitting the active ingredient in the casing into the biostructure at an appropriate time interval. After all, the time of drug release can be controlled through the chemical composition of the biodegradable metal and the thickness of the capsule.

FIG. 5 is a sample photograph of a bioabsorbable drug transfer capsule for subcutaneous insertion according to the first embodiment in a preferred embodiment of the present invention, exemplifying a specific embodiment for the above-mentioned function.

As shown in the figure, in the case of the bioabsorbable drug transfer capsule for subcutaneous insertion according to the first embodiment of the present invention, the entire casing is made of a biodegradable metal, and a storage space capable of containing an active ingredient such as a vaccine is provided inside the casing. Prepare for.

In addition, the drug transfer capsule of the first embodiment is provided with a tip formed of a biodegradable metal having sufficient strength to pierce the skin, so that the capsule can penetrate into the subcutaneous structure. Has an advantageous structure. At this time, a launcher that pushes the drug transfer capsule of the above form into the inside of the skin can be further provided for a more advantageous insertion operation.

In addition, the casing of the capsule according to the present invention can have various sizes depending on the amount of the required active ingredient, and a plurality of capsule casings can be inserted if necessary.

Further, as shown in the figure, after the active ingredient such as a vaccine is filled in the containment space, the predetermined area of the casing is decomposed in the biological assembly by the plug that blocks the containment space before the communication portion is formed. Up to, the active ingredient in the containment space can be configured to be retained within the capsule.

A vaccination experiment was carried out on an experimental pig provided by the Livestock Science Institute with the sample produced through the first example, and the detailed contents thereof will be described later in Example 2.

FIG. 6 is a modified example of the first embodiment, exemplifying the form of the drug transfer capsule according to the second embodiment.

As shown, the drug transfer capsule according to the second embodiment is substantially similar to the first embodiment except for the form of the tip portion 10, and after injection of the active ingredient 2 such as a drug as shown in FIG. 6 (b). It has a structure provided with a storage space 22 blocked by a plug 7.

In the second embodiment, according to one object of the present invention, the decomposition region and the decomposition rate of the casing 1 are adjusted so that the active ingredient 2 flows out into the biological assembly at an appropriate time and at an appropriate speed. FIG. 6 (b) is a cross-sectional view for clearly showing the technical example for identifying the leakage point, and for clearly showing the internal structure of the drug transfer capsule according to the second embodiment, shows the casing. The point A where the partition wall 5 is formed thinner than the other regions in the partition wall 5 is shown.

That is, assuming that the entire region of the casing 1 is formed of a biodegradable metal having the same composition, under the same conditions in the living body, the point A where the thickness of the casing partition wall 5 is the thinnest in the decomposition process of the casing 1 is located. The fastest communication and the formation of leak holes as intended can be adjusted to allow the active ingredient 2 to flow out at a desired rate.

Further, in this embodiment, the case where the accommodation space 22 is one is illustrated, but the accommodation space 22 can be divided into two or more spaces, and at this time, the leakage point of each accommodation space is described above. By constructing such a method, the active ingredient 2 can be sequentially leaked into the living body at a desired time point.

That is, the leakage of the active ingredient is such that the relevant point of the accommodation space 22 including the thinnest partition is the primary leakage point, and the relevant point of the accommodation space 22 including the next thinnest partition is the secondary leakage point. Since the procedure can be set, for example, in the case of a vaccine that requires three inoculations, a drug transfer capsule according to the present invention containing two containment spaces 22 is inserted into the bioorganization and at the same time one inoculation. If this is done, the active ingredient will be leaked at the primary leak point after the intended specific period, and the effect of the second inoculation will be exhibited, and after that, the active ingredient will be leaked at the secondary leak point after the specific period. This completes the complete antibody formation process on the third inoculation.

On the other hand, an example of adjusting the leakage amount and timing of the active ingredient by adjusting the thickness of the casing partition wall 5 has been described with reference to FIG. Through several years of research by the inventor, we have secured a theoretical and experimental basis for adjusting the rate of decomposition of biodegradable metals in vivo by adjusting the composition of the metal, thereby ensuring a specific region of casing 1. By making the biodegradable metal composition of the or point different, the primary and nth leak points are set in exactly the same way as the thickness adjustment described above, and the active component 2 in each of the divided accommodation spaces 22 is set. Of course, can be configured to leak at a suitable rate at a desired time point.

7 to 8 are views of a preferred embodiment of the present invention for a third embodiment, FIG. 7 is a drawing of a bioabsorbable drug transfer capsule for subcutaneous insertion according to a third embodiment of the present invention, and FIG. It is a drawing for demonstrating the process for applying a bioabsorbable drug transfer capsule for subcutaneous insertion to a living body according to 3rd Example of the invention.

As described in detail above and in FIG. 7, the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention can be provided in the form of a combination of a biodegradable metal and a biodegradable polymer material.

That is, as shown in FIG. 7, the tip portion 10 and the nodule portion 20 having a structure capable of piercing the skin in the form of a tip are manufactured of a biodegradable metal having a relatively high strength according to the chemical formula 1, and said. An inflatable portion 30 made of a biodegradable polymer material made of a soft material can be bonded between the tip portion 10 and the nodule portion 20.

In the case of the first embodiment and the second embodiment described above, since the entire material is made of a solid metal material, casings 1 having various sizes are provided depending on the amount of the active ingredient 2 that needs to be injected into the living body. If the amount of the active ingredient 2 is large, the size of the casing 1 becomes large, or the number of casings 1 to be inserted increases, which not only makes the insertion work difficult, but also burdens the living body. There is a disadvantage that it may become.

Therefore, when the bioabsorbable drug transfer capsule for subcutaneous insertion according to the present invention is constructed with a structure as in the third embodiment, most of the active ingredient 2 can be contained in the soft swelling portion 30. Therefore, the advantage that the size at the time of insertion can be reduced is further added, and the above-mentioned advantage that the leakage time and amount of the active ingredient 2 can be set by adjusting the decomposition rate of the metal region is applied as it is. can do.

That is, as the inflatable portion 30, a tubular or bosom-shaped polymer material capable of elastic expansion can be applied, but even if it is not highly elastic, if it is a soft material, it will be crumpled or compressed. Polydioxanone (PDO), polylactic acid (PLA), poly-L-lactic acid (polydioxanone (PDO), polylactic acid (PLA), poly-L-lactic acid ( PLLA), polyglycolic acid (PGA), glycolide-L-lactic acid copolymer (PGLA), glycolide-caprolactone copolymer (PGCL) and the like can be applied.

As shown in FIG. 7, the drug transfer capsule according to the third embodiment of the present invention has a structure that prevents the active ingredient in the inflated portion 30 from flowing out, and the active ingredient 2 is contained in the casing 1 of the drug transfer capsule. Configuration for injecting, configuration for preventing the injected active ingredient 2 from coming off, configuration for piercing the skin, configuration for cooperating with a separate insertion means when inserting into the skin, metal area and swelling part Includes a configuration for the 30 to combine and the like.

First, as a configuration for injecting the active ingredient 2 into the casing 1 of the drug transfer capsule, a drug or the like is injected as shown in FIG. 7 (b), which is a cross-sectional view of a third embodiment. It is provided with an injection port 21 capable of capable. The injection of the drug through such an injection port 21 can be performed by various methods, but as will be described later with reference to FIG. 8 and the like, a method through an existing syringe 100 and the like is also possible.

On the other hand, the function of preventing the injected active ingredient 2 from coming out is achieved by the backflow preventing means 25 located inside the nodule portion 20. A widely known backflow prevention valve structure can be applied to the backflow prevention means 25, and in the simplest form, a backflow prevention function by an elastic membrane that elastically closes the injection port can also be applied.

The function for piercing the skin is achieved by the tip 10 with a tip.

The method of piercing the skin with such a morphological feature of the tip 10 and locating the capsule according to the present invention in the biological assembly can be achieved by a separate auxiliary tool, and as one example, a syringe is used. The process of inserting the capsule according to the third embodiment of the present invention into the skin is shown in FIG. At this time, the injection port 21 and the backflow prevention means 25 described above are configured to accommodate the injection needle 110 of the syringe 100, and the end portion of the injection needle 110 is particularly anchored inside the tip portion 10. By providing the injection needle anchoring portion 11 of the above, the insertion direction of the tip portion 10 into the skin can be stably fixed when the syringe 100 is attached.

As shown in FIG. 7B, the structure for connecting the metal region and the inflatable portion 30 is such that both ends of the tubular inflatable portion 30 are located outside one end of the tip portion 10 or the nodule portion 20. It can also be done by fixing the end of the inflatable portion 30 with, which can also be provided with a biodegradable metal material, forcible fitting of a fixing ring, and the like.

FIG. 8 is a drawing illustrating a process for applying the drug transfer capsule according to the embodiment of FIG. 7 in vivo. As shown in the drawing, in the case of the casing 1 shown in FIG. 7, injection of a general syringe 100 is performed. It has a shape corresponding to the needle 110.

Therefore, as shown in FIG. 8A, first, the casing 1 is coupled to the injection needle 110 in a state where the syringe 100 is filled with an appropriate amount of the active ingredient 2 to be injected.

Then, as shown in FIG. 8B, in a state where the casing 1 and the syringe 100 are connected, the insertion process is performed by piercing the skin using the tip end portion 10 of the casing 1.

When the casing 1 is inserted at the desired biostructure inside the skin, the piston of the syringe 100 is pushed to start injecting the active ingredient 2 into the accommodation space of the casing 1 as shown in FIG. 8 (c). ..

When the injection of the active ingredient 2 is completed, the inflated portion 30 of the drug transfer capsule according to the third embodiment is in the fully inflated state, and as shown in FIG. 8 (d), if the syringe 100 is removed, FIG. The active ingredient 2 is held in a state of being injected into the casing 1 by the backflow prevention means 25 described above.

After that, after a predetermined period of time has elapsed, the leakage of the active ingredient 2 at the desired primary leakage point begins, so that the effect is similar to that of the secondary inoculation of the vaccine.

FIG. 9 is a drawing of a bioabsorbable drug transfer capsule for subcutaneous insertion according to the fourth embodiment as a modification of the third embodiment shown in FIGS. 7 to 8.

The fourth embodiment shown in FIG. 9 comprises two bulging portions 30, which include a nodule portion 20, a terminal nodule portion 20a, and an intermediate nodule portion 20b.

Such a configuration is meaningful as an example for realizing the secondary and tertiary inoculation effects at once at predetermined period intervals without a separate booster inoculation by being inserted at the time of the primary inoculation.

Embodiments of the Invention In the following, examples of experiments conducted together with the research of the present invention will be described in detail in order to further clarify the effects of the above-mentioned configurations and the substantial configurations in various examples.

[Experimental example]
Hereinafter, the present invention will be described in more detail through experimental examples. These experimental examples are for exemplifying the present invention, and it is obvious to those having ordinary knowledge in the art that the scope of the present invention is not construed to be limited by these experimental examples.

Experimental Example 1: Evaluation of metal sheet decomposition rate

Samples 1-9: Metal sheet made of magnesium or zinc as the main material

A metal sheet (casting in a high-frequency melting furnace and then extruding at a speed of 0.1 mm / s to a left-right width of 60 mm and 1.5 mm) was produced with the composition (% by weight) shown in Table 1 below.

Pure metal containing unavoidable impurities generated during manufacturing

After immersing the metal sheet produced in Samples 2 to 7 in an udiometer containing a biological copying solution having the composition shown in Table 2, the decomposition rate was evaluated by the amount of hydrogen generated by the immersion time, and the result was evaluated. It is shown in FIG.

As shown in FIG. 4, _{the metal sheets of Samples 2 to 5 in which the Mg 2} Ca phase was not generated showed the amount of hydrogen gas generated by stable decomposition, but the samples 6 and 7 in _{which the Mg 2 Ca phase was generated showed the amount of hydrogen gas generated.} It was confirmed that the amount of hydrogen gas generated in the metal sheet was definitely higher than that in the other examples, and that the decomposition rate was increased. Through this, it was confirmed that the decomposition rate of the biodegradable metal can be adjusted by adjusting the composition of Chemical Formula 1.

Experimental example 2: Pig foot-and-mouth disease antibody formation experiment

[Primary antibody formation experiment]

A 9-week experiment was conducted using 16 8-week-old pigs of the same week age at the end of 2016, and the group was divided into the injection injection group by the conventional method and the group into which the drug transfer capsule according to the first embodiment of the present invention was inserted. The degree of antibody formation was comparatively measured in the control group separately.

An ELISA method is applied as an immunoquantification method for confirming the formation of a vaccine antibody (SP), and when the value is 50 or more, it is confirmed that the antibody is positive.

The drug transfer capsule had pure magnesium, a containment space of 3.40 pie, a size of 54.70 mm, and each carried 0.5 cc of the same type of vaccine.

Test livestock: 16 8-week-old pigs, 9-week experiment

-Group 1 (5 animals): Foot-and-mouth disease inoculation method (muscle) application (8, 12 weeks after birth)

-Group 2 (5 animals): Foot-and-mouth disease inoculation method (subcutaneous) application (8, 12 weeks after birth)

-Group 3 (3 animals): Foot-and-mouth disease inoculation method (subcutaneous) + 4-week capsule inoculation (8 weeks after birth)

-Group 4 (3 animals): Foot-and-mouth disease inoculation method (subcutaneous) + 2-week capsule inoculation (8 weeks after birth)

The numerical values arranged in the above table are shown graphically through FIG. As can be seen from the table and the graph of FIG. 10, sufficient antibody formation was confirmed in groups 3 and 4 to which the capsules according to the present invention were applied, and in particular, in the case of group 4 to which the degraded capsules were applied for 2 weeks, the conventional injection was performed. A higher antibody-forming effect than the method was confirmed. In the case of the injection method, it was confirmed that the immunoquantitative value after the second inoculation was slightly lower, whereas the results in Group 3 and Group 4 led to a slight increase. It is presumed that this is because the necessary vaccine is not leaked all at once but is leaked little by little, or there are various causes such as an increasing effect due to by-products produced in the process of decomposing biodegradable metals.

[Secondary antibody formation experiment]

Experiments were conducted using 14 8-week-old pigs of the same week-old age at the end of 2017 as shown in Table 4 below. The degree of antibody formation was comparatively measured in the control group divided into the conventional injection injection group and the group into which the drug transfer capsule according to the first embodiment of the present invention was inserted.

An ELISA method was applied as an immunoquantification method for confirming the formation of vaccine antibody (SP).

The drug transfer capsule had pure magnesium, a containment space of 3.40 pie, a size of 54.70 mm, and each carried 0.5 cc of the same type of vaccine.

The numerical values arranged in the table are shown graphically through FIG.

As can be seen from the graph of FIG. 11, sufficient antibody formation was confirmed in the group 1 to which the capsule according to the present invention was applied as in the control group subjected to the muscle inoculation method (8 weeks, 12 weeks), and in particular, the degraded capsule was used. In the case of Group 4 applied for 2 weeks, a higher antibody-forming effect than the conventional injection method was confirmed.

Although the specific part of the content of the present invention has been described in detail through preferred examples and the like, such a specific technique is merely a preferred embodiment for a person having ordinary knowledge in the technical field to which the present invention belongs. It is self-evident that the scope of the invention is not limited. Therefore, the substantial scope of the invention should be defined by the claims and their equivalents.

1 Casing 2 Active ingredient 5 Casing bulkhead
7 Plug 10 Tip 11 Injection needle anchoring 20 Nodule
21 Inlet 22 Containment space
25 Backflow prevention means 30 Inflatable part 100 Syringe 110 Injection needle

Claims (13)

To form a casing space for accommodating the active ingredient in order to be inserted into the subcutaneous biological structure to transmit the active ingredient, and to block the accommodating space from the outside so that the active ingredient is not leaked to the outside. Consists of including a casing
The casing absorbs water so that it can be absorbed into the biological structure after allowing the active ingredient in the accommodation space to flow out by being decomposed in the biological structure. Bio-absorbent drug transfer capsule for subcutaneous insertion, made of sex material. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 1, wherein the bioabsorbable material of the casing contains a biodegradable metal represented by the following chemical formula 1.
[Chemical formula 1]
Mg _a Zn _b X _c
(In Chemical Formula 1, a, b and c are% by weight of each component, a + b + c = 100% by weight, and a or b is in the range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, 0 ≦ c ≦ 40. Largest, X is one or more selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.) In the above chemical formula 1, a, b and c are% by weight of each component, and a + b + c = 100% by weight. I) 90 ≦ a ≦ 100, 0 ≦ b ≦ 10, 0 ≦ c ≦ 40 or ii) 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 40, and X is one or more selected in the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 2. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 2, wherein the biodegradable metal is pure Mg containing unavoidable impurities. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 2, wherein the biodegradable metal is pure Zn containing unavoidable impurities. At least a part of the casing is a metal region formed of the biodegradable metal, and the active ingredient in the accommodation space leaks to the outside in the metal region in the process of decomposing the bioabsorbable material. The primary leak point is formed, and the nth-order leak point (n is 2 or more) in which the leakage of the active ingredient after the leakage of the primary leak point occurs sequentially at other points of the casing including the metal region. The bioabsorbable drug transfer capsule for subcutaneous insertion according to any one of claims 2 to 5, wherein an integer of) can also be formed. The primary leak point or the nth leak point is a component composition of the biodegradable metal that causes two or more metal phases according to the chemical formula 1 to generate a galvanic circuit to accelerate the decomposition rate. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 6, wherein is formed by appropriately arranging the metal region. The primary leakage point or the nth leakage point is the point where the thickness of the casing wall is the thinnest by adjusting the thickness of the casing wall between the accommodation space of the casing and the outside. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 6, wherein the nth-order leak point is sequentially formed according to the thickness of the casing wall so as to be a leak point. The accommodation space including the primary leak point or the nth leak point forms an isolated space in the casing in which the active ingredient cannot communicate, corresponding to the respective primary leak point or nth leak point. 6. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 6. A tip formed of the biodegradable metal, an inflated portion formed of a soft biodegradable polymer material, and at least one formed of the biodegradable metal connected to at least one end of the inflated portion. Consists of including one or more nodules
The swelling portion is formed in a tube or a pocket shape capable of accommodating the active ingredient inside, and the tip portion or the nodule portion is connected to both ends so as to communicate with each other. The bioabsorbable drug transfer capsule for subcutaneous insertion according to any one of 2 to 5. The tip has a tip that can pierce the skin in the process of being inserted subcutaneously.
The subcutaneous insertion according to claim 10, wherein the nodule portion is provided with an injection port capable of injecting the active ingredient and a backflow prevention means for preventing the injected active ingredient from flowing out to the outside. For bioabsorbable drug transfer capsules. The injection port of the nodule has a tubular shape through which the injection needle can penetrate so that it can be used in a form attached to the injection needle of a drug injection means such as a syringe. It comprises a backflow prevention valve structure such as an elastic membrane that prevents the active ingredient injected from the drug injection means from flowing out after the injection needle is removed.
The inside of the connecting portion of the tip portion with the inflated portion is provided with an injection needle anchoring portion that allows the skin insertion direction of the tip portion to be stably fixed by mounting the injection needle. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 11. The swelling part is polydioxanone (PDO), polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), glycolide-L-lactic acid copolymer (PGLA) and glycolide-caprolactone copolymer. The bioabsorbable drug transfer capsule for subcutaneous insertion according to claim 10, characterized in that it is one or more biodegradable polymer materials selected in the group consisting of (PGCL).

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